Docket Number EPA-HQ-OPP-2011-0105 

www.regulations.gov 

Amitrole Summary Document 

Registration Review: Initial Docket 

June 2011 

 

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TABLE OF CONTENTS 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 12 

III. Summary of Data Gaps 17 

__________________________________________________________________ 

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position based on the following documents: 

1. Registration Review – Problem Formulation for the Ecological Risk and Drinking Water 

Exposure Assessments for Amitrole (PC Code 004401; DP Barcode D390513). M. 

Wagman. June 10, 2011. 

2. Amitrole: Human Health Risk Scoping Document in Support of Registration Review. D. 

Drew. June 13, 2011. 

3. BEAD Chemical Profile for Registration Review: Amitrole: PC Code 004401. K. RienzoStack. May 25, 2011. 

4. Amitrole Use and Usage Information. August 19, 2010.

5. Amitrole Review of Human Incidents. K. Oo. March 1, 2011. 

These and other supporting documents for the amitrole registration review case may be found in 

the docket EPA-HQ-OPP-2011-0105 at http://www.regulations.gov.
4

I. PRELIMINARY WORK PLAN – AMITROLE

Introduction: 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The Agency will consider benefits information and data as required by FIFRA. The 

public phase of registration review begins when the initial docket is opened for each case. The 

docket is the Agency’s opportunity to state what it knows about the pesticide and what additional 

risk analyses and data or information it believes are needed to make a registration review 

decision. After reviewing and responding to comments and data received in the docket during 

this initial comment period, the Agency will develop and commit to a final work plan and 

schedule for the registration review of amitrole. 

Amitrole is a triazole-containing herbicide registered for use for outdoor general weed control to 

non-agricultural rights-of-way, industrial and construction sites, fencerows, and other 

uncultivated areas. Tolerances are not currently established for amitrole as there are no 

registered food or feed uses. There are currently no residential uses for amitrole. One of 

amitrole’s degradates, cyanamide – a separate pesticide active ingredient, may be of 

toxicological concern because available data indicate that cyanamide may be more toxic to 

aquatic organisms than the parent amitrole. Amitrole was first registered in 1948, and the 

Reregistration Eligibility Decision (RED) for Amitrole was completed in August 1996. 

Anticipated Risk Assessment and Data Needs:

The Agency anticipates the need to require data and to conduct a comprehensive ecological risk 

assessment, including an endangered species assessment, for all uses of amitrole and its 

degradates of concern. For human health, EPA anticipates the need to require data and to 

conduct a dietary (drinking water only) assessment and revised occupational risk assessments 

during registration review. If toxicological endpoints or points of departure are revised based on 

the data that are required for registration review, they will be considered in the new assessment, 

as well as any changes to the standard operating procedures or default exposure assumptions. 

Below is a summary of the issues relevant to the registration review of amitrole. 
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Ecological Risk: 

• The most recent comprehensive ecological risk assessment for amitrole was completed in 

support of the 1996 Amitrole RED. 

• An updated ecological risk assessment of all registered uses of amitrole and its 

degradates of concern will be conducted during registration review. The new assessment 

will incorporate the most up-to-date modeling methodologies, updated toxicological 

endpoints, and data submitted under the anticipated registration review data call-in. 

• A risk assessment that supports a complete endangered species determination has not 

been conducted for amitrole. The ecological risk assessment planned during registration 

review will allow the Agency to determine whether amitrole’s use has “no effect” or 

“may affect” federally listed threatened or endangered species (listed species) or their 

designated critical habitats. When an assessment concludes that a pesticide’s use “may 

affect” a listed species or its designated critical habitat, the Agency will consult with the 

U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), 

as appropriate. 

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the Services regarding the effects of over 

350 pesticides, including amitrole, on over 200 endangered and threatened species 

throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 

11-00293 (N.D.Cal.). 

• Data gaps exist in the environmental fate and toxicity databases for amitrole. EPA is 

currently reviewing six of the environmental fate studies identified below. Although 

these studies have been submitted to EPA, they will be considered data gaps at this time 

until they have been reviewed and found to be acceptable. EPA anticipates requiring the 

following guideline studies for use in conducting a complete ecological risk assessment, 

including an endangered species assessment, for the registration review of amitrole. 

Environmental Fate Guidelines: 

835.1410 – Volatility, laboratory 

835.2240 – Photodegradation in water1

835.2410 – Photodegradation in soil1

835.4100 – Aerobic soil metabolism1

835.4200 – Anaerobic soil metabolism 

835.4300 – Aerobic aquatic metabolism1

835.4400 – Anaerobic aquatic metabolism1

 

1

 Data are currently in review for these studies. Although these studies have been submitted to EPA, they will be 

considered data gaps at this time until the data have been reviewed and found to be acceptable. 
6

835.6100 – Terrestrial field dissipation1

[If data currently in review are determined to be acceptable, only the 

Environmental chemistry analytical methods and independent laboratory 

validation (ILV) for soil portions of this guideline would be required.] 

835.62002 – Environmental chemistry analytical methods and independent laboratory 

validation for water 

835.7100 – Ground water monitoring 

Ecotoxicological Guidelines: 

850.1350 – Aquatic invertebrate life cycle toxicity (saltwater, mysid shrimp, A. 

bahia)

850.1400 – Fish early life stage toxicity test, TGAI (freshwater, rainbow trout)

850.1400 – Fish early life stage toxicity test, TGAI (saltwater, sheepshead minnow)

850.2100 – Acute avian oral toxicity test using a passerine species, TGAI

850.4100 – Seedling Emergence, Tier II, TEP

850.4150 – Vegetative Vigor, Tier II, TEP 

Ecotoxicological Guidelines with amitrole’s degradate, cyanamide: 

850.1350 – Aquatic invertebrate life cycle toxicity (saltwater, mysid shrimp, A. 

bahia)

850.1400 – Fish early life stage toxicity test (freshwater, rainbow trout)

850.1400 – Fish early life stage toxicity test (saltwater, sheepshead minnow)

• One of amitrole’s degradates, cyanamide, itself is a plant growth regulator and pesticide 

active ingredient (PC Code 014002) currently undergoing registration review (Docket ID: 

EPA-HQ-OPP-2007-1014). Since cyanamide may be a major degradate of amitrole and 

the available data indicate that cyanamide may be more toxic to aquatic organisms than 

the parent amitrole, the three studies listed above are anticipated to be needed for use in 

conducting the planned registration review risk assessment for amitrole. 

The 2007 cyanamide problem formulation noted data gaps, but did not request data, for 

chronic estuarine/marine fish and invertebrate tests. The problem formulation noted that 

submission of these studies would reduce uncertainty, and in the absence of these data, 

effects to salt water organisms would be assumed equivalent to effects on freshwater 

species. The more widespread nature of the amitrole use pattern, versus the limited use 

of cyanamide on fruit trees, makes it more likely that cyanamide exposure to estuarine 

organisms will occur as a result of amitrole use. Therefore, given the data gaps for 

cyanamide and their potential effects on the ecological risk assessment for amitrole, EPA 

anticipates requiring a chronic estuarine/marine invertebrate and fish early life stage 

studies to be conducted with cyanamide as listed above. 

 

2

 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical 

methods and ILV portions of this guideline for water. 
7

The freshwater fish early life stage study (MRID 44076701) cited in the 2007 cyanamide 

problem formulation is classified as supplemental because effects were observed at all 

test concentrations and a no observed effect concentration (NOEC) was not observed. A 

NOEC is needed for risk assessment purposes, and therefore, these data are anticipated as 

being needed to reduce uncertainties in the risk assessment for amitrole 

Lastly, seedling emergence and vegetative vigor studies for cyanamide were required in 

the cyanamide registration review data call-in (RR-014002-28861) issued on January 6, 

2010. Due to the parent/degradate relationship between amitrole and cyanamide, these 

data may need to be considered during the registration review of amitrole. 

• Please refer to the June 10, 2011 document Registration Review – Problem Formulation 

for the Ecological Risk and Drinking Water Exposure Assessments for Amitrole (PC 

Code 004401; DP Barcode D390513) in the amitrole registration review docket (EPAHQ-OPP-2011-0105) for a detailed discussion of the anticipated risk assessment and data 

needs. 

Human Health Risk:

• The most recent comprehensive human health risk assessment for amitrole was 

conducted in December 1995. Toxicological endpoints were revised in May 1996, and 

the changes were incorporated into the 1996 Amitrole RED. 

• A dietary (food) exposure assessment is not anticipated as being needed during 

registration review because there are currently no registered food or feed uses for 

amitrole, and dietary (food) exposure is not expected based on registered uses.

• A drinking water dietary assessment for amitrole has not previously been conducted, and 

EPA anticipates conducting one during registration review.

• Since there are no residential uses and no anticipated residential exposures from amitrole, 

residential handler and post-application exposure assessments are not anticipated as being 

needed during registration review. 

• Updates to the occupational handler exposure assessments using current standard 

operating procedures and exposure assumptions are expected during registration review 

for currently registered amitrole products. It is anticipated that inhalation exposures will 

be assessed. However, a dermal exposure assessment is not anticipated because the 

endpoint selected from the dermal developmental toxicity study (1,500 mg/kg/day) is 

above the exposure expected based on the currently registered uses of amitrole. In 

addition to updating the three occupational handler scenarios assessed in the 1995 risk 

assessment, a handler assessment is expected to be performed during registration review 

for mixing, loading, and applying water-dispersible granules. This scenario has not been 

previously assessed. 

• Occupational post-application inhalation exposures are expected to be negligible because 

re-entry is restricted until sprays have dried, and volatilization will be negligible. The 
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dermal endpoint for an occupational post-application dermal exposure assessment is 

above the exposure expected based on the currently registered uses of amitrole. For these 

reasons, occupational post-application assessments for amitrole are not anticipated during 

registration review. 

• EPA anticipates the need to require the following data for use in reevaluating and 

updating the human health toxicity profile for the registration review of amitrole: 

870.1300 – Acute inhalation toxicity - rat 

870.3465 – 90-day inhalation - rat 

870.6200 – Acute and subchronic neurotoxicity - rat 

870.7800 – Immunotoxicity 

• Please refer to the June 13, 2011 document Amitrole: Human Health Risk Scoping 

Document in Support of Registration Review in the amitrole registration review docket 

(EPA-HQ-OPP-2011-0105) for a detailed discussion of the anticipated risk assessments 

and data needs. 

Endocrine Disruptor Screening Program: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its reregistration decision, EPA reviewed these data and selected 

the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard 

database. However, as required by FFDCA section 408(p), amitrole is subject to the endocrine 

screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 
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chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Amitrole is not 

among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for amitrole. For further information on 

the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/. 

Timeline:

EPA has created the following estimated timeline for the completion of amitrole’s registration 

review. 

Registration Review for Amitrole – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period 2011 – June 

Close Public Comment 2011 – August 

Case Development 

Final Work Plan 2011 – November 

Issue DCI 2012 – July – Sept. 

Data Submission 2014 – July – Sept. 

Open Public Comment Period for Draft Risk Assessments 2016 – Jan. – March 

Close Public Comment Period 2016 – April – June 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2016 – July – Sept. 

Close Public Comment Period 2016 – Oct. – Dec. 

Registration Review Decision and Begin Post-Decision Follow-up 2017 

Total (years) 6 

Guidance for Commenters: 

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the amitrole case. 

Trade Irritants: 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

Because amitrole is not registered for food/feed uses in the U.S., it has no U.S. tolerances. 

However, amitrole does have registered food uses in other counties. 
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Water Quality: 

Amitrole is not identified as a cause of impairment for any water bodies listed as impaired under 

section 303(d) of the Clean Water Act3

. In addition, no Total Maximum Daily Loads (TMDL) 

have been developed for amitrole4

. More information on impaired water bodies and TMDLs can 

be found at the Agency’s website5. The Agency invites submission of water quality data for this 

pesticide. To the extent possible, data should conform to the quality standards in Appendix A of 

the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water 

Quality Data in OPP’s Registration Review Risk Assessment and Management Process6

 in order 

to ensure they can be used quantitatively or qualitatively in pesticide risk assessments. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to amitrole compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

Other Information: 

By a separate letter, EPA has asked the amitrole technical registrant, Nufarm Americas Inc., to 

provide additional information on several previously submitted environmental fate studies. This 

information is needed for use in conducting a full review of the submitted data. 

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including any species-specific ecological 

determinations. The Agency is interested in obtaining the following information: 

1. confirmation on the following label information 

a. sites of application 

b. formulations 

c. application methods and equipment 

d. maximum application rates 

e. frequency of application, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use 

2. use or potential use distribution (e.g., acreage and geographical distribution of relevant 

use sites) 

 

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

4

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

5 http://www.epa.gov/owow/tmdl/

6 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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3. use history 

4. median and 90th percentile reported use rates (lbs ai/1000 sq ft) from usage data – 

national, state, and county 

5. application timing (date of first application and application intervals) – national, state, 

and county 

6. sub-county use site location data 

7. usage/use information for non-agricultural uses 

8. directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs ai/acre) from usage data – county 

b. median and 90th percentile number of applications – county 

c. total pounds per year – county 

d. the year the pesticide was last used in the county/sub-county area 

e. the years in which the pesticide was applied in the county/sub-county area 

9. typical application interval (days) 

10. state or local use restrictions 

11. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency 

12. monitoring data 

Next Steps: 

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a Final Work Plan for the registration 

review of amitrole. 
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II. FACT SHEET 

 

Background Information: 

• Amitrole registration review case number: 0095. 

• Amitrole PC code: 004401. 

• Amitrole CAS No.: 61-82-5. 

• Amitrole was first registered for use in the United States in 1948.

• The Amitrole RED was completed in August 1996.

• The technical registrant for amitrole is Nufarm Americas, Inc. 

• There are currently two end-use products and one technical product registered for 

amitrole. There are no active state-specific Special Local Need registrations or 

emergency exemptions. 

• As a result of the product reregistration process following the Amitrole RED, one product 

was cancelled in 1997 and two were reregistered in 2006. 

• Because there are no food or feed uses of amitrole, there are no tolerances established for 

this chemical. 

• Pesticide Re-evaluation Division, Chemical Review Manager: Monica Wait, 

wait.monica@epa.gov 

• Registration Division, Product Manager: Kable (Bo) Davis, davis.kable@epa.gov

Use & Usage Information: (For additional details on label rates and use sites, refer to Amitrole 

Use and Usage Information, August 19, 2010 and the BEAD Chemical Profile for Registration 

Review: Amitrole, May 25, 2011, in the amitrole registration review docket EPA-HQ-OPP2011-0105.) 

• Amitrole is an herbicide registered for use outdoors for general weed control to nonagricultural rights-of-way, industrial and construction sites, fencerows, and other 

uncultivated areas. Amitrole is registered for use along highways, railroads, public 

utilities, and industrial areas and may be used to keep these areas vegetation free for 

maximum visibility, safety, and to prevent the growth of potentially combustible weeds. 

• There are no registered food or feed uses of amitrole, and there are no residential or 

homeowner uses. 

• Amitrole end-use products are formulated as a water-dispersible granule and in water 

soluble bags (formulation type not specified on label). 

• Amitrole is applied by fixed-boom sprayers attached to tractors, trucks, or railroad 

wagons. 

• Amitrole was previously classified as a “restricted use” pesticide, but that classification 

was rescinded following incorporation of mitigation measures, use cancellations, and 

product cancellations specified by the Amitrole RED. 
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• EPA does not have a current nationwide estimate of amitrole usage. Data from the 

California Department of Pesticide Regulation indicated that less than 10 pounds were 

applied per year from 2006 to 2008 for the state of California only. 

• Although dated, the 1996 Amitrole RED estimated that national usage of amitrole was at 

or below 40,000 to 60,000 pounds of active ingredient per year. 

Ecological Risk Assessment Status:

Please refer to the Registration Review – Problem Formulation for the Ecological Risk and 

Drinking Water Exposure Assessments for Amitrole (PC Code 004401; DP Barcode D390513), 

June 10, 2011 for a detailed discussion of the key findings of the most recent ecological risk 

assessments. A summary follows: 

 

Summary of Risks: 

• The most recent comprehensive ecological risk assessment for amitrole was completed in 

support of the 1996 Amitrole RED. 

• The ecological risk assessment conducted in support of the RED concluded that 

maximum labeled use rates of amitrole for registered uses at that time exceeded acute 

endangered species levels of concern (LOCs) for birds feeding on short and tall grass and 

broadleaf plants and for small mammals consuming short grass and insects. Since there 

was no mortality at the highest concentration in the avian dietary test, amitrole was 

considered to represent low acute risk to birds. 

• The RED concluded that no acute LOCs were exceeded for freshwater fish or 

invertebrates, but risk to estuarine/marine invertebrates exceeded the acute endangered 

species LOC of 0.05. 

• Chronic risk to mammals exceeded the chronic LOC of 1.0 for small herbivores 

consuming short grass, seeds and insects, while chronic risk to birds, fish and aquatic 

invertebrates was not assessed due to a lack of data. 

Human Health Risk Assessment Status: 

Please refer to Amitrole: Human Health Risk Scoping Document in Support of Registration 

Review, June 13, 2011 for a detailed discussion of the key findings of the most recent human 

health risk assessment. A summary follows: 

Hazard Characterization:

• The primary target organ is the thyroid. Data from short-term and chronic studies 

indicate that effects will appear in the thyroid at lower dose levels than any other target 

organ. 
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• Amitrole was previously classified as a probable human carcinogen by the Office of 

Pesticide Programs (OPP) Carcinogenicity Peer Review Committee. This carcinogen 

classification was based on thyroid tumors in both sexes of multiple strains of rats, 

pituitary tumors in rats, and liver tumors in two strains of mice. In 2006, OPP’s Cancer 

Assessment Review Committee (CARC) re-evaluated the carcinogenic potential of 

amitrole and reclassified amitrole as “Not Likely To Be Carcinogenic To Humans At 

Doses That Do Not Alter Rat Thyroid Hormone Homeostasis.” (See the Amitrole: 

Human Health Risk Scoping Document in Support of Registration Review for further 

details.) 

• Based on the overall weight of the evidence found in the genotoxicity database, amitrole 

is not considered to be a mutagen or to cause thyroid follicular cell carcinogenesis 

through a mutagenic mode of action. 

Dietary (Food and Drinking Water):

• A dietary exposure assessment was not conducted during the 1995 amitrole risk 

assessment because amitrole had no registered food uses. 

• A drinking water assessment for amitrole has not previously been conducted. 

Residential (Non-occupational): 

 

• All homeowner products were voluntarily cancelled following the 1984 Notice of Special 

Review for amitrole. Therefore, residential handler and post-application exposure 

assessments were not required or conducted for the 1995 risk assessment. 

Aggregate: 

• An aggregate risk assessment typically evaluates the combined risk from dietary 

exposure (food plus drinking water) and any residential uses. However, since there were 

no residential or dietary exposures for amitrole, an aggregate assessment was not 

conducted during the most recent assessment 

• Amitrole is a triazole-derived herbicide. A triazole-metabolite aggregate assessment has 

been completed for the triazole class of chemicals. Amitrole has not been included in this 

assessment, because it is not expected to form the free triazole, triazole-alanine, or 

triazole acetic acid metabolites. Furthermore, the toxicity profile of amitrole is distinct 

from the triazole metabolites, producing primarily thyroid hyperplasia in chronic studies. 

Conversely, the triazole metabolites produce neurotoxicity, developmental toxicity, blood 

cell toxicity, and skeletal deformations. 

Occupational Handlers:

• The 1995 occupational handler risk assessment indicated that the margins of exposure for 

short- and intermediate-term inhalation exposures at baseline protection (i.e., no 
15

respirator) were not of concern to the Agency. Because the endpoint selected from the 

dermal developmental toxicity study (1,500 mg/kg/day) was above the exposure expected 

based on the registered uses of amitrole, a dermal exposure assessment was not required 

or conducted as part of the 1995 risk assessment. 

Occupational Post-application: 

• A quantitative occupational post-application assessment was not conducted during the 

1995 risk assessment. Amitrole is used in areas, such as rights-of-way, industrial areas, 

and other non-crop areas, where frequent or routine entry by persons who may contact 

treated surfaces is unlikely. EPA determined that such post-application exposures do not 

appear to pose an unreasonable risk to persons entering treated areas, as long as entry is 

not permitted immediately after application. To prevent immediate re-entry, the current 

labels specify, “Do not enter or allow employees to enter treated areas until sprays have 

dried.” 

Reliance on Human Studies: 

• Past amitrole risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED) and the Agricultural Reentry Task Force (ARTF) Database. EPA has 

reviewed all the studies supporting these multi-pesticide generic exposure databases, and 

has found no clear and convincing evidence that the conduct of any of them was either 

fundamentally unethical or significantly deficient relative to the ethical standards 

prevailing at the time the research was conducted. All applicable requirements of EPA’s 

Rule for the Protection of Human Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies. 

Cumulative: 

• For the purposes of this registration review, EPA has not assumed nor determined that 

amitrole has a common mechanism of toxicity with other substances. For information 

regarding EPA’s efforts to determine which chemicals have a common mechanism of 

toxicity and to evaluate the cumulative effects of such chemicals, see the policy 

statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found 

to have a common mechanism on EPA’s website at: 

http://www.epa.gov/pesticides/cumulative/. If, in the future, the Agency determines that 

new information on amitrole is available that could potentially impact a cumulative risk 

assessment and result in a risk of concern, the Agency will revisit the need for a 

cumulative risk assessment. 
16

Incidents: 

• EPA’s preliminary review of the Ecological Incident Information System (EIIS, version 

2.1) and the Avian Monitoring Information System (AIMS) on April 19, 2011, indicated 

that no “major” fish, wildlife, or plant incidents associated with the use of amitrole have 

been reported to the Agency. Additionally, no incidents involving amitrole have been 

reported to the Agency in aggregated incident reports which are intended to capture 

“minor” fish, wildlife, and plant incidents. However, for various reasons, such as 

decreased monitoring and sublethal effects which are not easily observed, the absence of 

reported incidents should not be construed as the absence of incidents. 

• A summary report listing human incidents for amitrole has been provided in the docket 

item entitled Amitrole Review of Human Incidents, March 1, 2011. The evaluation of the 

OPP Incident Data System (IDS) indicated no incidents identified in the United States 

from 2002 thru 2010 for the single chemical amitrole. In Aggregate IDS, from 2002 to 

February 2011, there are five cases reported for amitrole. Aggregate IDS only includes 

counts of incidents classified as “minor,” “unknown,” or “no effects,” and no additional 

details about the incidents are provided. For amitrole, the low frequency and severity of 

incident cases suggests a low potential for exposure to this chemical. There does not 

appear to be a concern at this time that would warrant further investigation.

Tolerances and International Harmonization: 

• Because there are no registered food or feed uses for amitrole, no tolerances are currently 

established. 

Data Call-In Status: 

• A generic data call-in (GDCI-004401-17739) was issued in December 1996 as a result of 

the data requirements listed in the 1996 Amitrole RED. All of the data requirements 

from the RED data call-in have been fulfilled or waived. 

Labels: 

 

• A list of registration numbers for the amitrole case is provided below, and the labels can 

be obtained from the Pesticide Product Label System (PPLS) website7

. 

Registration 

# Registration Name Company Name % Active Ingredient 

33688-5 Technical Amitrole Nufarm SA 92.7 

33688-6 Maxata Branch Industrial Herbicide Nufarm SA 88.2 

33688-10 Maxata Water Soluble Granules Nufarm SA 86.2 

 

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 http://oaspub.epa.gov/pestlabl/ppls.home 
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III. SUMMARY OF DATA GAPS – AMITROLE 

The table below summarizes all anticipated data needs for amitrole in Section I, of this document 

(Preliminary Work Plan), the Registration Review – Problem Formulation for the Ecological 

Risk and Drinking Water Exposure Assessments for Amitrole (PC Code 004401; DP Barcode 

D390513) dated June 10, 2011, and the Amitrole: Human Health Risk Scoping Document in 

Support of Registration Review dated June 13, 2011. 

Guideline 

Number Anticipated Data Need Test 

Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

835.1410 Volatility, laboratory TEP 12 

835.2240 Photodegradation in water8 TGAI 12 

835.2410 Photodegradation in soil8 TGAI 12 

835.4100 Aerobic soil metabolism8 TGAI 24 

835.4200 Anaerobic soil metabolism TGAI 24 

835.4300 Aerobic aquatic metabolism8 TGAI 24 

835.4400 Anaerobic aquatic metabolism8 TGAI 24 

835.6100 Terrestrial field dissipation8, 9 TEP 24 

835.6200 

Environmental chemistry analytical methods and 

independent laboratory validation (ILV) for 

water10

TGAI 12 

835.7100 Ground water monitoring TEP 12 

850.1350 Aquatic invertebrate lifecycle (saltwater, mysid 

shrimp, A. bahia) TGAI 12 

850.1350 Aquatic invertebrate lifecycle (saltwater mysid 

shrimp, A. bahia) for the degradate cyanamide TGAI 12 

850.1400 Fish early life stage toxicity test (freshwater, rainbow 

trout) TGAI 12 

850.1400 Fish early life stage toxicity test (freshwater, rainbow 

trout) for the degradate cyanamide TGAI 12 

850.1400 Fish early life stage toxicity test (saltwater, 

sheepshead minnow) TGAI 12 

850.1400 Fish early life stage toxicity test (saltwater, 

sheepshead minnow) for the degradate cyanamide TGAI 12 

850.2100 Avian oral acute toxicity test using a passerine species TGAI 12 

850.4100 Seedling Emergence, Tier II TEP 12 

 

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 Data are currently in review for these studies. Although these studies have been submitted to EPA, they will be 

considered data gaps at this time until the data have been reviewed and found to be acceptable. 9

 If data currently in review are determined to be acceptable, only the Environmental chemistry analytical methods 

and ILV for soil portions of this guideline would be required. 

10 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical 

methods and ILV portions of this guideline for water. 
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Guideline 

Number Anticipated Data Need Test 

Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

850.4150 Vegetative Vigor, Tier II TEP 12 

870.1300 Acute inhalation toxicity - rat TGAI 8 

870.3465 90-day inhalation - rat11 TGAI 24 

870.6200 Acute and subchronic neurotoxicity - rat TGAI 24 

870.7800 Immunotoxicity Study TGAI 12 

 

11 The timeframe for this study may be able to be reduced from 90 days to 28 days if the data plateaus during the 

test, or if exposure potential is not expected to exceed 28 days.